The lung-immune prognostic index (LIPI) to predict early mortality among patients affected by advanced solid cancers under immune-checkpoint inhibitors treatments.
Authors: Andrea De Giglio, Daria Maria Filippini, Veronica Mollica, Karim Rihawi, Francesca Comito, Francesca Carosi, Andrea Marchetti, Ilaria Ricciotti, Francesco Gelsomino, Elisabetta Nobili, Barbara Melotti, Francesca Sperandi, Francesco Massari, Maria A. Pantaleo, Andrea Ardizzoni
Journal: Journal of Clinical Oncology (2023)

e14602 Background: The introduction of immune-checkpoint inhibitors (ICI) revolutionized the treatment of several advanced neoplasms. Unfortunately, a considerable rate of patients experiences early death (≤ 90 days). Transversal prognostic factors for early death under ICI single agents or in combinations with other agents are lacking. The lung immune prognostic index (LIPI) includes pretreatment derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) levels and demonstrated an affordable prognostic value in advanced solid tumors ICI-treated. Methods: We performed a retrospective study including 498 patients affected by advanced solid malignancies treated with ICI or in combination with other agents. We explored prognostic factors associated with early mortality (≤ 90 days). Then, we tested the LIPI score to predict early mortality risk through Cox-regression models and ROC curve analysis. Results: Most patients included were males (63.2%) with ECOG PS 0-1 (85.9%). Non-small cell lung cancer was the most frequent malignancy (80.3%), followed by head-neck (10.7%), genitourinary (5%), and gastrointestinal (4%) tumors. 324 (68.1%) patients received ICI single agent, while 152 (31.9%) ICI plus other agents (chemotherapy, tyrosine kinase inhibitors), primarily as upfront treatment (60.5%). The LIPI score was assessable for 305 patients. The median overall survival was 8.9 months (95%CI, 7.6-11.6), while the median progression-free survival was 4.5 months (95% 3.8-5.6). In a multivariable model, ECOG PS 2 (HR 1.85, p = 0.013) and intermediate-high LIPI score (HR 2.50, p &lt; 0.001) were associated with increased death risk after adjusting for sex, age, histology, metastatic sites, and line of treatment. In the same model, intermediate-high LIPI score (HR 2.45, p &lt; 0.001) and baseline liver metastasis (HR 1.87, p= 0.006) were associated with an increased risk of disease progression.118 patients (24.8%) experienced early mortality. ECOG PS 2 (HR 3.13, p&lt;0.001 ), &gt;3 metastatic sites (HR 1.93, p 0.018), baseline lung (HR 1.62, p 0.014) and liver (HR 1.74, p=0.01) metastases were associated to increased risk of 90-day death at univariate analysis. An intermediate-high LIPI score was associated with increased death risk in the univariate (HR 6.79, 95% CI, 3.24-14.22, p&lt;0.001) and multivariate (HR 6.84, 95% CI, 2.63-17.80, p&lt;0.001) assessments for 90-day mortality. ICI in combination with other agents was associated with reduced 90-day mortality risk also in the multivariable model (HR 0.46, 95% CI, 0.23-0.93, p=0.029). The Area Under the Curve for the LIPI score was 0.743 (95% CI, 0.68-0.80) for 90-day mortality prediction. Conclusions: We evidenced a considerable risk of early mortality under ICI-based strategies. The LIPI score predicted 90-day mortality risk regardless of the treatment and histotype.